Francesca Tomasi received her B.A. from the University of Chicago and currently does tuberculosis drug discovery research.
Whenever an infectious disease pops up somewhere, one of the first things epidemiologists want to know is how contagious the pathogen is. Understanding how quickly an illness may spread is essential in both deducing whether a public health intervention is warranted and coming up with a strategy. Mathematically, contagiousness is described by a number called R0, which is pronounced “R naught.” R0 tells you the average number of susceptible individuals who will contract an infection from one contagious person. Susceptible individuals are those who have not been infected by this agent and who have not been vaccinated against it.
There are three outcomes that stem from knowing a pathogen’s R0, each of which carries its own implications for whether an epidemic, a widespread occurrence of disease, will occur within a population.
For infectious diseases with an R0 greater than 1, appropriate measures need to be taken to curb a brewing outbreak. Suffice to say the larger the value of R0, the more difficult a pathogen is to control.
What goes into calculating a pathogen’s R0? The three main factors are infectious period, contact rate, and mode of transmission. The longer someone is contagious, the higher the chances that person will spread their illness to more people. Similarly, the more frequently a contagious person interacts with susceptible individuals, the more people are likely to get infected. This plays into visible versus invisible illness too: if someone is visibly ill, they are more likely to stay at home (or in a hospital) and avoid contact with the outside world. Furthermore, if somebody is diagnosed with an infectious disease, they may even be quarantined, a practice that dates back thousands of years, before people even knew what caused communicable diseases. The term “quarantine” itself comes from the Venetian dialect of the Italian phrase quaranta giorni, which means forty days. During the Black Death in the 14th century, ships were isolated for 40 days before their passengers could enter cities. Lastly, how a disease spreads will dictate how contagious it is. For instance, something that spreads through the air – like the flu – does not necessarily require physical contact and thus spreads quickly and easily. On the other hand, diseases like HIV that are transmitted by bodily fluids, are harder to catch and spread.
Let’s look at some common infectious diseases and their R0 values:
Just as with any tool, R0 carries its own limitations. In the event of vector-borne diseases like malaria, it is difficult to predict frequency of mosquito bites and boil it down to an average. Furthermore, R0 is often attributed as a threshold rather than an absolute quantity. Regardless, it is helpful to understand disease dynamics when informing public health interventions in the event of an outbreak.
Nick Deason received his B.S. in Biology from the University of Notre Dame and currently studies the spread of drug-resistant malaria.
The scale of our universe is astounding. The Milky Way alone is up to 100 trillion times the size of our sun. When you try to compare the size of subatomic particles to the observable universe, you must abandon words and turn to scientific notation to describe the numbers involved.
As a biologist studying infectious diseases, I often struggle to comprehend the scale of the microbes that live inside us and make us sick. Prompted by this ignorance, I set out to identify the largest and smallest viruses, bacteria, and parasites that call humans home. While not quite as dramatic as the difference between subatomic particles and astronomical bodies, the range of sizes of human pathogens is astonishing in its own right, with a size difference of more than one billion-fold from smallest to largest. If the smallest human virus were enlarged to the size of a tennis ball, the longest parasitic worm would easily wrap around the circumference of Earth’s equator. With this range of proportions in mind, let’s start with our smallest pathogens and make our way up.
The Nano: Prions, Viroids, and Viruses
At the small end of the spectrum, things are a bit hazy. For one, the infectious agents involved at this level – prions, viroids, and viruses – are not necessarily living organisms. Prions (such as the causative agent of Mad Cow Disease) are simply misfolded proteins that cause a chain reaction of more protein misfolding. Viroids consist only of RNA (genetic material similar in structure to DNA) that replicates using host enzymes. Meanwhile, viruses are semi-living packages of genetic material and protein that reproduce inside of organisms’ cells.
The smallest of these agents, prions, may be as few as 5 to 10 nanometers (nm) in length (for reference, a nanometer is one billionth of a meter, or roughly the length of 3 carbon atoms). However, the caveat is that prions often cling together to form large aggregates of proteins, and so the size of infectious prion particles is often much larger than a single protein.
Viroids are infectious pieces of RNA that also replicate using host enzymes. They cause disease by interfering with normal host cell function through a process called gene silencing. However, all known viroids are in plants, so I largely ignored them for this article, but if you’re interested, you can read more about Hepatitis D, which is a human disease caused by a viroid-like mechanism.
Viruses are much more familiar to the average person and can cause diseases as common as the seasonal flu or as rare and deadly as Ebola. Viruses are made up of DNA or RNA surrounded by a protective protein coat. Some may also have an outer lipid layer that protects the virus and functions in pathogenesis. While larger than viroids or single proteins, viruses are still very small. The smallest human-infecting viruses that I came across in my search belong to a group called parvoviruses, of which I chose parvovirus B19 as an example to focus on. At a mere 23-26nm in diameter, parvovirus B19 can only be seen with powerful electron microscopes. Somehow, this virus is nonetheless able to pack several thousand base pairs of DNA into its small protein capsid. Normally, DNA is about 2nm wide, but in this case the virus can save some precious space because it’s genome is actually comprised of single stranded DNA.
Parvovirus B19 is most notable for causing bright red rashes in infected children, leading to the term “slapped check syndrome.” However, immune-compromised people, such as those with HIV infection, can have more serious manifestations of disease.
Surprisingly, it’s not just viruses that make their living at this nanometer scale. I was astounded to learn that a bacterium in the urinary tract of humans called Mycoplasma genitalium can measure as little as 200nm in length. It also has one of the smallest genomes of any cellular organism, with around 580,000 base pairs. This made it the ideal organism to use in The Minimal Genome Project, in which scientists deleted various genes in M. genitalium and discovered a minimum of 382 that were needed to sustain life. In regards to public health, this bacterium causes urethritis and sometimes more serious pathology in the reproductive organs of both men and women.
The last stop on our tour of the nanoscale are poxviruses: the largest viruses that infect humans. A familiar example is variola virus, the causative agent of smallpox. This enveloped virus may be up to 350nm at its longest point, making it a behemoth in the virus world. Amazingly though, there are viruses that dwarf even variola, although they almost always exclusively infect amoebas. The largest of all, Pithovirus, measures 1500nm in length. Finally, there is some debate as to whether a virus called Mimivirus causes pneumonia in humans. If confirmed, this 400+ nm long virus would replace poxviruses on our list.
The Micro: Bacteria and Parasites
A micrometer (μm) is 1000 times longer than a nanometer. In other words, it takes 1000nm to equal 1μm. The organisms measured in micrometers are typically single cells, such as bacteria and small eukaryotes. The latter category includes microsporidium, which are single-celled infectious fungi. When they infect humans, they replicate inside of our cells, which necessitates them being very small. Typically, the spores of the 15 human-infecting microsporidium species measure 1-4μm in length. Disease manifestation includes diarrhea and wasting, most commonly in AIDS patients. A similarly-sized intracellular parasite is the malarias, whose “ring stages” are about 1-2μm in diameter.
The largest human-infecting bacteria are probably spirochetes. These long, thin, and spiral shaped prokaryotes cause diseases like syphilis, Lyme disease, and maybe even dementia. Featured below is Borrelia burgdorferi, the causative agent of Lyme disease. While less than a micrometer wide, these spirochetes can be more than 20μm in length. For reference, this is almost as long as a human skin cell.
The Macro: Bugs and Worms
Of course, there are infectious agents that we can see with our own eyes. These include parasites like fleas, mites, and worms. None come close to the size of the beef tapeworm, however. Obtained by consuming undercooked beef, these worms can grow to be over 22m long (that’s over 70ft!) in our intestines, although they are typically less than 10m long in most infections.
Thinking back to our smallest pathogen, Parvovirus B19, we see the huge range of sizes that infectious agents can come in. Each organism’s body size is adapted to its specific home. Intercellular viruses are small, constrained by the size of our own cells, while worms that live in our intestines, like the tapeworm, can afford to be much larger. As the parasitologist Dickson Despommier always says: “Successful systems attract parasites.” In the case of humans, we are so successful that viruses, bacteria, and parasites of all sizes have evolved to find a home in our bodies.
Francesca Tomasi received her B.A. from the University of Chicago and currently researches tuberculosis drug targets in search for novel antibiotics.
Proteins are essential components in all forms of carbon-based life, capable of serving just about every function imaginable. From providing physical structure to a cell, to orchestrating complex metabolic networks, our bodies need hundreds of thousands of different types of proteins to survive.
So how do we study them? To begin, scientists typically need to isolate a protein of interest. For example, say someone wants to investigate a bacterial protein as a new drug target. They want to isolate that molecule and test whether different drugs successfully bind to and inhibit its function.
To do so, scientists use SDS-PAGE gel electrophoresis, a popular technique that allows the separation of biological molecules.
Say you have a massive box filled with knotted ropes, but you just want to take out a single shoelace from the box. If you were looking for a specific, 15” shoelace, how would you distinguish it from a similar-looking one that’s longer or shorter if they are all knotted up? You would have to dump the box on the floor, detangle its contents, and pick out your shoelace.
Proteins exist in their own sort of knotted mess, complex three-dimensional conformations that render them uniquely capable of carrying out a very specific process. So just like it’s easier to find a specific string in a tangled mess after untangling and sorting everything out, it is easier to pick out a protein of interest by “untangling” all the proteins in a solution and sorting them out by length.
In SDS-PAGE, proteins are linearized by a detergent called SDS (which stands for sodium dodecyl sulfate) that also gives them a negative charge. Once proteins are injected into a gel (the starting point of this time-lapse video), an electric current is turned on, which allows them to travel across the gel. Larger proteins require a larger “pull” to move than smaller ones, so everything moves at a different rate down the gel.
A researcher knows the size of a specific protein of interest by studying its genetic code and the amino acids that make it up; it is therefore easy to pinpoint its location on a gel, using a template ladder (the left-most lane in this video), which acts as a size key.